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https://www.readbyqxmd.com/read/28320757/additional-candidate-genes-for-human-atherosclerotic-disease-identified-through-annotation-based-on-chromatin-organization
#1
Saskia Haitjema, Claartje A Meddens, Sander W van der Laan, Daniel Kofink, Magdalena Harakalova, Vinicius Tragante, Hassan Foroughi Asl, Jessica van Setten, Maarten M Brandt, Joshua C Bis, Christopher O'Donnell, Caroline Cheng, Imo E Hoefer, Johannes Waltenberger, Erik Biessen, J Wouter Jukema, Pieter A F M Doevendans, Edward E S Nieuwenhuis, Jeanette Erdmann, Johan L M Björkegren, Gerard Pasterkamp, Folkert W Asselbergs, Hester M den Ruijter, Michal Mokry
BACKGROUND: As genome-wide association efforts, such as CARDIoGRAM and METASTROKE, are ongoing to reveal susceptibility loci for their underlying disease-atherosclerotic disease-identification of candidate genes explaining the associations of these loci has proven the main challenge. Many disease susceptibility loci colocalize with DNA regulatory elements, which influence gene expression through chromatin interactions. Therefore, the target genes of these regulatory elements can be considered candidate genes...
April 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/28304160/nucleosome-histone-tail-conformation-and-dynamics-impacts-of-lysine-acetylation-and-a-nearby-minor-groove-benzo-a-pyrene-derived-lesion
#2
Iwen Fu, Yuqin Cai, Nicholas E Geacintov, Yingkai Zhang, Suse Broyde
Histone tails in nucleosomes play critical roles in regulation of many biological processes, including chromatin compaction, transcription, and DNA repair. Moreover, post-translational modifications, notably lysine acetylation, are crucial to these functions. While the tails have been intensively studied, how the structures and dynamics of tails are impacted by the presence of a nearby bulky DNA lesion is a frontier research area, and how these properties are impacted by tail lysine acetylation remains unexplored...
March 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28300215/chromatin-modification-contributes-to-the-expression-divergence-of-three-tags2-homoeologs-in-hexaploid-wheat
#3
Wei Zhang, Xiaoli Fan, Yingjie Gao, Lei Liu, Lijing Sun, Qiannan Su, Jie Han, Na Zhang, Fa Cui, Jun Ji, Yiping Tong, Junming Li
Plastic glutamine synthetase (GS2) is responsible for ammonium assimilation. The reason that TaGS2 homoeologs in hexaploid wheat experience different selection pressures in the breeding process remains unclear. TaGS2 were minimally expressed in roots but predominantly expressed in leaves, and TaGS2-B had higher expression than TaGS2-A and TaGS2-D. ChIP assays revealed that the activation of TaGS2-B expression in leaves was correlated with increased H3K4 trimethylation. The transcriptional silencing of TaGS2 in roots was correlated with greater cytosine methylation and less H3K4 trimethylation...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284913/higher-order-assembly-folding-the-chromosome
#4
REVIEW
Sven A Sewitz, Zahra Fahmi, Karen Lipkow
The linear molecules of DNA that constitute a eukaryotic genome have to be carefully organised within the nucleus to be able to correctly direct gene expression. Microscopy and chromosome capture methods have revealed a hierarchical organisation into territories, domains and subdomains that ensure the accessibility of expressed genes and eventually chromatin loops that serve to bring gene enhancers into proximity of their target promoters. A rapidly growing number of genome-wide datasets and their analyses have given detailed information into the conformation of the entire genome, allowing evolutionary insights, observations of genome rearrangements during development and the identification of new gene-to-disease associations...
March 8, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28264735/the-serine-106-residue-within-the-n-terminal-transactivation-domain-is-crucial-for-oct4-function-in-mice
#5
Atsushi Mitani, Atsushi Fukuda, Toshiyuki Miyashita, Akihiro Umezawa, Hidenori Akutsu
Pou5f1/Oct4 is a key transcription factor for the induction of pluripotency and totipotency in preimplantation mouse embryos. In mice, loss or gain of function experiments have demonstrated an important role for Oct4 in preimplantation and developmental ability. In this study, using mouse preimplantation embryos as a model for the evaluation of Oct4 function, we constructed Oct4 overexpression embryos with various mutations at the N-terminal transactivation domain. Developmental competency and molecular biological phenotypes depended on the type of mutation...
March 7, 2017: Zygote: the Biology of Gametes and Early Embryos
https://www.readbyqxmd.com/read/28263316/single-molecule-sequencing-and-chromatin-conformation-capture-enable-de-novo-reference-assembly-of-the-domestic-goat-genome
#6
Derek M Bickhart, Benjamin D Rosen, Sergey Koren, Brian L Sayre, Alex R Hastie, Saki Chan, Joyce Lee, Ernest T Lam, Ivan Liachko, Shawn T Sullivan, Joshua N Burton, Heather J Huson, John C Nystrom, Christy M Kelley, Jana L Hutchison, Yang Zhou, Jiajie Sun, Alessandra Crisà, F Abel Ponce de León, John C Schwartz, John A Hammond, Geoffrey C Waldbieser, Steven G Schroeder, George E Liu, Maitreya J Dunham, Jay Shendure, Tad S Sonstegard, Adam M Phillippy, Curtis P Van Tassell, Timothy P L Smith
The decrease in sequencing cost and increased sophistication of assembly algorithms for short-read platforms has resulted in a sharp increase in the number of species with genome assemblies. However, these assemblies are highly fragmented, with many gaps, ambiguities, and errors, impeding downstream applications. We demonstrate current state of the art for de novo assembly using the domestic goat (Capra hircus) based on long reads for contig formation, short reads for consensus validation, and scaffolding by optical and chromatin interaction mapping...
March 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28258094/nucleome-analysis-reveals-structure-function-relationships-for-colon-cancer
#7
Laura Seaman, Haiming Chen, Markus Brown, Darawalee Wangsa, Geoff Patterson, Jordi Camps, Gilbert S Omenn, Thomas Ried, Indika Rajapakse
Chromosomal translocations and aneuploidy are hallmarks of cancer genomes; however, the impact of these aberrations on the nucleome (i.e., nuclear structure and gene expression) are not yet understood. Here, the nucleome of the colorectal cancer cell line HT-29 was analyzed using chromosome conformation capture (Hi-C) to study genome structure, complemented by RNA sequencing (RNA-seq) to determine consequent changes in genome function. Importantly, translocations and copy number changes were identified at high resolution from Hi-C data and the structure-function relationships present in normal cells were maintained in cancer...
March 3, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28251841/topologically-associated-domains-a-successful-scaffold-for-the-evolution-of-gene-regulation-in-animals
#8
REVIEW
Rafael D Acemel, Ignacio Maeso, José Luis Gómez-Skarmeta
The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs)...
March 2, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28230735/new-evidence-for-the-theory-of-chromosome-organization-by-repetitive-elements-core
#9
Shao-Jun Tang
Repetitive DNA elements were proposed to coordinate chromatin folding and interaction in chromosomes by their intrinsic homology-based clustering ability. A recent analysis of the data sets from chromosome-conformation-capture experiments confirms the spatial clustering of DNA repeats of the same family in the nuclear space, and thus provides strong new support for the CORE theory.
February 20, 2017: Genes
https://www.readbyqxmd.com/read/28228067/epigenetic-characteristics-of-the-mitotic-chromosome-in-1d-and-3d
#10
Marlies E Oomen, Job Dekker
While chromatin characteristics in interphase are widely studied, characteristics of mitotic chromatin and their inheritance through mitosis are still poorly understood. During mitosis, chromatin undergoes dramatic changes: transcription stalls, chromatin-binding factors leave the chromatin, histone modifications change and chromatin becomes highly condensed. Many key insights into mitotic chromosome state and conformation have come from extensive microscopy studies over the last century. Over the last decade, the development of 3C-based techniques has enabled the study of higher order chromosome organization during mitosis in a genome-wide manner...
April 2017: Critical Reviews in Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28215225/transcription-factors-in-breast-cancer-lessons-from-recent-genomic-analyses-and-therapeutic-implications
#11
E Zacksenhaus, J C Liu, Z Jiang, Y Yao, L Xia, M Shrestha, Y Ben-David
Multiplatform genomic analyses have identified 93 frequently altered genes in breast cancer. Of these, as many as 49 genes are directly or indirectly involved in transcription. These include constitutive and inducible DNA-binding transcription factors (DB-TFs, 13 genes), corepressors/coactivators (14 genes), epigenetic (10), and mediator/splicing/rRNA (3) factors. At least nine additional genes are immediate upstream regulators of transcriptional cofactors. G:profiler analysis reveals that these alterations affect cell cycle, development/differentiation, steroid hormone, and chromatin modification pathways...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28174273/h3k4me3-induces-allosteric-conformational-changes-in-the-dna-binding-and-catalytic-regions-of-the-v-d-j-recombinase
#12
John Bettridge, Chan Hyun Na, Akhilesh Pandey, Stephen Desiderio
V(D)J recombination is initiated by the recombination-activating gene (RAG) recombinase, consisting of RAG-1 and RAG-2 subunits. The susceptibility of gene segments to cleavage by RAG is associated with histone modifications characteristic of active chromatin, including trimethylation of histone H3 at lysine 4 (H3K4me3). Binding of H3K4me3 by a plant homeodomain (PHD) in RAG-2 stimulates substrate binding and catalysis, which are functions of RAG-1. This has suggested an allosteric mechanism in which information regarding occupancy of the RAG-2 PHD is transmitted to RAG-1...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28174238/functional-characterisation-of-cis-regulatory-elements-governing-dynamic-eomes-expression-in-the-early-mouse-embryo
#13
Claire S Simon, Damien J Downes, Matthew E Gosden, Jelena Telenius, Douglas R Higgs, Jim R Hughes, Ita Costello, Elizabeth K Bikoff, Elizabeth J Robertson
The T-box transcription factor (TF) Eomes is a key regulator of cell fate decisions during early mouse development. The cis-acting regulatory elements that direct expression in the anterior visceral endoderm (AVE), primitive streak (PS) and definitive endoderm (DE) have yet to be defined. Here, we identified three gene-proximal enhancer-like sequences (PSE_a, PSE_b and VPE) that faithfully activate tissue specific expression in transgenic embryos. However, targeted deletion experiments demonstrate that PSE_a and PSE_b are dispensable and only the VPE is required for optimal Eomes expression in vivo Embryos lacking this enhancer display variably penetrant defects in anterior-posterior axis orientation and DE formation...
February 7, 2017: Development
https://www.readbyqxmd.com/read/28132686/decreased-stard10-expression-is-associated-with-defective-insulin-secretion-in-humans-and-mice
#14
Gaelle R Carrat, Ming Hu, Marie-Sophie Nguyen-Tu, Pauline Chabosseau, Kyle J Gaulton, Martijn van de Bunt, Afshan Siddiq, Mario Falchi, Matthias Thurner, Mickaël Canouil, Francois Pattou, Isabelle Leclerc, Timothy J Pullen, Matthew C Cane, Priyanka Prabhala, William Greenwald, Anke Schulte, Piero Marchetti, Mark Ibberson, Patrick E MacDonald, Jocelyn E Manning Fox, Anna L Gloyn, Philippe Froguel, Michele Solimena, Mark I McCarthy, Guy A Rutter
Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family...
February 2, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28131315/retrieving-chromatin-patterns-from-deep-sequencing-data-using-correlation-functions
#15
Jana Molitor, Jan-Philipp Mallm, Karsten Rippe, Fabian Erdel
Epigenetic modifications and other chromatin features partition the genome on multiple length scales. They define chromatin domains with distinct biological functions that come in sizes ranging from single modified DNA bases to several megabases in the case of heterochromatic histone modifications. Due to chromatin folding, domains that are well separated along the linear nucleosome chain can form long-range interactions in three-dimensional space. It has now become a routine task to map epigenetic marks and chromatin structure by deep sequencing methods...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28118111/identification-of-the-amino-acid-residues-responsible-for-stable-nucleosome-formation-by-histone-h3-y
#16
Tomoya Kujirai, Naoki Horikoshi, Yan Xie, Hiroyuki Taguchi, Hitoshi Kurumizaka
Histone H3.Y is conserved among primates. We previously reported that exogenously produced H3.Y accumulates around transcription start sites, suggesting that it may play a role in transcription regulation. The H3.Y nucleosome forms a relaxed chromatin conformation with flexible DNA ends. The H3.Y-specific Lys42 residue is partly responsible for enhancing the flexibility of the nucleosomal DNA. To our surprise, we found that H3.Y stably associates with chromatin and nucleosomes in vivo and in vitro. However, the H3...
January 24, 2017: Nucleus
https://www.readbyqxmd.com/read/28108933/modelling-genome-wide-topological-associating-domains-in-mouse-embryonic-stem-cells
#17
Y Zhan, L Giorgetti, G Tiana
Chromosome conformation capture (3C)-based techniques such as chromosome conformation capture carbon copy (5C) and Hi-C revealed that the folding of mammalian chromosomes is highly hierarchical. A fundamental structural unit in the hierarchy is represented by topologically associating domains (TADs), sub-megabase regions of the genome within which the chromatin fibre preferentially interacts. 3C-based methods provide the mean contact probabilities between chromosomal loci, averaged over a large number of cells, and do not give immediate access to the single-cell conformations of the chromatin fibre...
January 20, 2017: Chromosome Research
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#18
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28097824/mechanisms-of-metabolic-memory-and-renal-hypoxia-as-a-therapeutic-target-in-diabetic-kidney-disease
#19
REVIEW
Yosuke Hirakawa, Tetsuhiro Tanaka, Masaomi Nangaku
Diabetic kidney disease (DKD) is a worldwide public health problem. The definition of DKD is being under discussion. Although the term DKD was originally defined as "kidney disease specific to diabetes", DKD frequently means chronic kidney disease (CKD) with diabetes mellitus and includes not only classical diabetic nephropathy, but also kidney dysfunction due to nephrosclerosis and other causes. Metabolic memory plays a crucial role in the progression of various complications of diabetes, including DKD. The mechanisms of metabolic memory in DKD are supposed to include advanced glycation end products, DNA methylation, histone modifications, and non-coding RNA including microRNA...
January 17, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28094382/the-supercoiling-state-of-dna-determines-the-handedness-of-both-h3-and-cenp-a-nucleosomes
#20
R Vlijm, S H Kim, P L De Zwart, Y Dalal, C Dekker
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core...
January 17, 2017: Nanoscale
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